Parental illness and/or death from HIV/AIDS has a profound and lasting impact on a child's psychosocial well-being, potentially challenging the basic needs for survival and compromising the child's future. Therefore, the impact of parental HIV/AIDS on children needs to be treated from both a public health and a developmental perspective. Compelling evidence in early childhood development in the face of adversity has revealed the critical importance of resilience (e.g., successful adaptation despite risk and adversity) in laying the foundation for successful adjustment later in life. However, to date the role of a resilience-based approach among children affected by HIV is hypothesized but not evidence-based. In this application, we propose to develop a theory-guided, resilience-based, multimodal intervention by culturally adapting and integrating components from three SAMHSA model programs which show strong evidence in promoting protective factors among young children (Specific Aim #1). The adaptation process will be informed by 1) the comprehensive qualitative and quantitative data collected from our previous NIH-funded longitudinal study in rural China during the past 5 years; 2) our 18 years' experience in developing and adapting effective HIV behavioral prevention programs in a broad range of cultural settings including China; and 3) our on-going research collaboration with Chinese investigators and local communities. The multimodal intervention will include three approach levels: the individual child (peer-group activities), the family (caregiver parenting skill training), and the local community (community advocacy). The short, medium, and long-term efficacy of the Child-Caregiver-Advocacy-Resilience [ChildCARe] intervention to improve health and psychosocial well-being of children will be evaluated over 36 months through a cluster randomized controlled trial (Specific Aim #2). Eight hundred HIV/AIDS-affected children (8 to 11 years of age) and their primary caregivers will be recruited from 80 villages in central China where we have built a strong research infrastructure and community collaboration during our previous study. The primary outcome measures for the children will include physical health, mental health, growth and development, school performance, and a biological indicator of neurobiological stress response (salivary cortisol). The outcome measures at caregiver level will include parenting style, parental engagement, and mental health well-being. The changes at the community level will be measured using children's and caregivers' perceptions of social support and HIV-related public stigma. We will also examine the potential mechanism through which the ChildCARe intervention is exerting its impact by identifying improvement in protective factors and other individual and contextual factors that potentially mediate or moderate the intervention effect (Specific Aim #3). This proposed project will examine whether the multilevel protective factors we identified in our initial project are amenable to intervention and whether their hypothesized changes explain improvement in children outcomes. This application provides an alternative to a deficit paradigm of intervention and shifts our conceptualization from pathology to resilience. The combination of self-report data and data from laboratory tests of salivary cortical will provide an opportunity to examine whether the prevention impact of a resilience-based intervention can extend to domains beyond behaviors.